[gcanyon]

As is often the case, the title is hyperbolic. The discovery applies to 20% of tumors, and "one of cancer's significant defenses" or "a key weakness of cancer" would be more accurate.

That said, I'll happily take "we discovered a key weakness in 20% of cancers," please and thank you.

[jibal]

Not hyperbolic, just incomplete ... this drug inhibits the KRAS mutation that is the "master switch" for 90% of pancreatic cancers and 50% of colon cancers. KRAS was considered "undruggable" so this is a huge breakthrough which is why oncologists gave a standing ovation for nearly a minute in the middle of a talk, with some of them in tears.

[asveikau]

20% is still a huge number. (Your comment also acknowledges this of course. That just popped out at me.)

[inglor_cz]

Aren't those 20 per cent of tumors more concentrated on the "intractable" side? If so, then the hyperbole is forgivable.

[cschmidt]

It does seem like those 20% are exactly on the nasty side. So even more impressive.

[DataDaoDe]

I'm no expert, and don't know if it applies in this case, but for a cancer I had (lymphoma) I was told that aggressive can often be easier to treat or "cure" (as defined by survival rates, etc.) since it also can often be hit more brutally by the treatments.

Anyway, since many in my family have died from this horrible cancer, its fantastic news to hear of any improvements there.

[jibal]

Sorry, it does not apply ... this drug inhibits (for the first time) the KRAS mutation (previously considered "undruggable") that is the primary cause of 90% of pancreatic cancers and 50% of colon cancers.

[DataDaoDe]

No reason to be sorry, that sounds like this is even better news then :)

[jibal]

I just meant that this doesn't apply to lymphoma, which is not caused by KRAS.

[inglor_cz]

Lymphoma is a bit of an outlier. In the case of lymphoma, more aggressive types indeed respond better to treatment, and given that we are now fairly good at treating lymphoma, that translates to good outcomes.

That is not true for most cancers, though.

[basisword]

What does this mean in layman's terms? How will this potentially help me if I get cancer?

[epistasis]

Cancer is not one thing, it's a huge zoo of many many many ways that cells start to break the social contract and divide in an uncontrolled manner.

One of the most commonly observed broken mechanisms is mutation in the gene KRAS that turns this on/off growth switch into the permanently on position.

This has been known for decades, of course. And there have been huge amounts of effort to try to develop drugs that target KRAS in cancer, but for decades it's always been thought of as 'undruggable' because of the difficulty of finding any molecules that would affect it.

This new drug, that finally treats KRAS mutated cancers, goes about it in a new way. Instead of trying to gum up the works of a single protein by sticking a small chemical in it, it effectively "glues" the KRAS protein to another protein, CypA, which keeps the switch away from reaching the normal areas where it's "on switch" activity works.

So this new drug means two things: 1) a lot of the most difficult to treat cancers are now far more treatable, and in the next 1-5 years clinical trials will tell us which cancers this particular drug works well for, 2) there's an entire new class of drug activity that everybody is chasing at this very moment, so in 5-25 years we'll likely have a huge number more of these sorts of treatments.

[inigyou]

How does it avoid targeting KRAS in healthy cells? Or is this another form of chemotherapy where we're trying our hardest to deliver the right amount of poison that kills the cancer before it kills the rest of you?

[epistasis]

It doesn't. Cancerous cells have a much higher dependency on RAS signaling to survive, so it's a drug that kills everything that's replicating via RAS signaling, much like standard chemotherapy kills cells in general that are reproducing more quickly.

However this is just the first version of the drug, it can be combined with other modalities to allow more selective targeting of cancer versus not cancer cells (e.g antibody-drug conjugation). And when used in earlier stage cancers, rather than the advanced cancers in this first clinical trial, there's the possibility of lower dosing that has less strong side effects.

This is just the first attack that has ever broken through to hit a key weakness of some cancers. It's the start of learning, a breakthrough that will launch refinements, enhancements, and a ton of innovation. That sort of innovation is sometimes derided as "me-too" drugs, and not meaningful, but some of the biggest advancements in cancer care have been from taking very hard to tolerate treatments and making them more tolerable and refined and better for patients, allowing longer and more thorough killing of cancer cells. I would expect we will see a lot of that here, as well as work towards combinations with other drugs.

[jibal]

This drug targets cells with a KRAS mutation that locks the KRAS switch in the ON state, driving uncontrolled growth. Cells with this mutation are abnormal and predisposed to becoming cancer ... so by definition are not healthy.

[oh_my_goodness]

>a lot of the most difficult to treat cancers are now far more treatable, and in the next 1-5 years clinical trials will tell us which cancers this particular drug works well for,

Can you help disambiguate this? Are there treatments now, or are there potential treatments with trials in 1-5 years?

[epistasis]

The next 1-5 years will tell us which cancers this new drug will work well on, right now it's only been tried in pancreatic cancer when people have failed their first treatment. The new drug from the article, daroxonrasib, has nine trials i see currently, here:

https://clinicaltrials.gov/search?intr=daraxonrasib&viewType...

The first two are the trial that just completed and showed success: people that have pancreatic cancer that failed other treatments, then a "trial" that is meant to give quick access to more people now that it's been shown to work.

Then there's a trial for using it as the first-line treatment for pancreatic cancer, one for lung cancer (NSCLC), and also various combinations with other drugs. I expect we'll see a ton of new trials registered in the coming year. Especially something in combination with colon cancer, because a common drug resistance mechanism in colon cancer is to develop KRAS mutation.

The thing is that we don't really know which cancers it will work well in until we try. And there's limited number of people with cancer that enter clinical trials, and we want to give each person their very best chance at survival, and then there's the massive expense of running the clinical trial itself, so learning happens slowly, one month of survival at a time, or one cancer recurrence at a time, or one death at a time. Patients that take part in clinical trials really are the heroes here. (Especially with the side effects of this new drug, which are horrible. It is a revolutionary drug, but we need to learn how to manage the other things it does as well, and that's going to take time.)

[shevy-java]

But that's not a cure. If they don't take that drug, assuming it works, they still have the original mutation in the cancer cells.

> Patients that take part in clinical trials really are the heroes here.

Are they?

To me personally, putting people into a permanent state of requiring drugs to survive, is not really cure. It's just maximizing income for those selling those drugs. And none of those drugs work exceedingly well; people still die, even if to other disease or frailties. I don't understand this hype in general.

[jmcgough]

I can understand being frustrated and cynical with the pharmaceutical industry, but I have never worked with a single doctor that approaches patient care with the goal of getting them "hooked" on something for life.

The pharmaceutical companies are not the ones making clinical decisions - in this case, it's a shared medical decision between a patient and their oncologist.

Having seen how horrific pancreatic cancer is, how difficult it is to treat, and the decades of slow research done by academic scientists to get to this point, I am elated that we have a tool to give patients more time with their families even if their cancer can't be "cured" with this particular drug.

This may seem unsatisfying, but it's real, measurable progress. KRAS has been known about since the earliest days of cancer research, so it's a true breakthrough to finally have a drug targeting it.

[michaelmrose]

Everyone dies. Dying 5 years later is a victory. I would go so far as saying if it was you or someone who you care about you would understand.

https://usafacts.org/articles/how-have-cancer-rates-changed-...

>However, even though the overall number of cases rises as the population grows, fewer people are getting and dying from cancer. Between 2000 and 2021, the incidence rate — or the rate of new cancer cases per 100,000 people — declined by 5.7%, while the annual mortality rate fell by 27.5%.

Cancer is a broad term encompassing many sorts of malfunction and nearly 40% of Americans will be diagnosed with it at some point because if you survive other hazards and maladies cancer is often what gets you.

[try_the_bass]

Wow, this is such a wildly pessimistic and cynical take. Are you okay?

> But that's not a cure. If they don't take that drug, assuming it works, they still have the original mutation in the cancer cells.

The person you're replying to called this out specifically:

> and also various combinations with other drugs.

Why do you think they try it in combination with other drugs? You might be right that this drug alone might not be a cure, but if it inhibits cancer growth, then it empowers other drugs to work more effectively.

> people still die

So what... We do nothing, then? This is your complaint? That we can't be immortal, so why bother trying to cure anything?

I don't understand your type in general.

[Spooky23]

My wife died of aggressive melanoma. Immunotherapy would likely have helped her if not for some complications that delayed it.

Today, only 4 years later, there are two therapies, one RNA based and one CART that would have been usable in her situation. She’d be alive today most likely.

Frankly, you have no idea what you’re talking about as you spew toxic bullshit. 5 year survival would meant being there for her son through high school. That survival rate was 65% in 2022 and closer to 80% now in recent trials.

Normally I’d scroll on, but in these degenerate days it is important to counter bullshit before it becomes policy.

[memonkey]

I think the meaning is that because we can see success with KRAS mutation of pancreatic cancer, we can now begin clinical trials for other cancers that may have KRAS mutation (colorectal, lung) and see if there is success there. If there is success in treating other cancers during clinical trials, it could be fast tracked through FDA to be more generally available and then become part of the national treatment option (ideally in 1-5 years after clinical trials).

[dyauspitr]

The golden panacea for this would be a gene editing mechanism that will work in every cell in the body. Once we have something we can do whole hog gene replacement, most human health problems would be solved forever.

[tremon]

For every cell mechanism that's being abused by cancer to fuel its growth, there are other cells in the body for which that mechanism is crucial for their correct functioning. Wholesale editing every cell in the body mostly guarantees that the patient does not die of cancer -- the cure will kill them before the disease does.

[dyauspitr]

Only cells that have the necessary signature get the edit

[Hendrikto]

So the exact opposite of what you said initially.

[redleggedfrog]

That was a really good summary, thank you.

[throwaway81523]

Can we end up with a situation like antimicrobial resistance, where cancer itself evolves to resist these new treatments?

[epistasis]

Yes, and one of the hallmarks of cancer is a removal of the usual DNA damage checkpoints. Cells have sensors that detect damaged DNA and stop cell division, and once that is gone evolution happens on an extremely accelerated times scale. In lung cancer, for example, we have developed entire series of drugs to go after successive resistance mutations inside the EGFR gene.

When we first started getting good at sequencing the DNA of tumors, I remember initial reports of taking samples across the 3D space of a tumor and finding great spatial heterogeneity in the tumor genomes.

I'm actually most excited for using this drug in combination with colon cancer, where KRAS mutation is a common drug resistance evolution in response to drugs that target the gene EFGR (though cancer researchers may all have their favorites to go after, colon cancer went after my family especially hard).

[nicwilson]

Absolutely, this is selective pressure at work on cells with malregulated genetics. Most typically, this is in the form of drug efflux pumps, but you can definitely get more specific resistances.

Ways to avoid specific resistance include multiple treatments simultaneously, since the probability of generating resistance to both is the product of the probability of resistance either.

[ulbu]

evolution is a wrong concept to approach it. cancer is not a separate life form, but a bug in the regeneration system of a complicated life form. it doesn’t exist outside of it, it cannot propagate.

[epistasis]

Cancer researchers generally refer to it as evolution, and I've never heard any complaints from the population geneticists or evo-devo folks about it, so I don't think it's a tremendously controversial way to talk about it. See for example

https://www.nature.com/articles/s41586-019-1907-7

[nly]

You might want to read this

https://en.wikipedia.org/wiki/HeLa

[8note]

the single celled dog might beg to differ.

sometimes a cancer can then survive on its own back as a single celled organism

[throwaway81523]

I've heard that some cancers spread by viruses. Viruses do evolve. No idea if that says anything about cancer evolving.

[pestatije]

thats environmental evolution...what happens here is cell "evolution" within a specific body

[basisword]

Thanks for the explanation!

[bad_username]

> Cancer is not one thing,

I know this is a popular "well actually" to do, but it is not always useful in a conversation. Yes, all cancers are different, but yes, cancer is also one thing: unchecked, harmful division of cells.

Bacteria are also all different, but still they are "one thing", and despite their diversity, antibiotics exist that can deal with many species of them at once. It is reasonable to talk about bacteria and antibacterial medications, it is also reasonable to talk about cancer and cancer treatment. I truly hope cancer will meet its "penicillin" one day (yes I know this is unlikely).

[dpark]

It seems relevant here because the question was “How will this potentially help me if I get cancer?” and the answer is “Not at all unless you get a particular form of cancer that this applies to”.

> Bacteria are also all different, but still they are "one thing", and despite their diversity, antibiotics exist that can deal with many species of them at once.

Except people don’t ask “what if I get bacteria” the way they ask about cancer. If the story was about a new antibiotic that only affected 20% of common infectious bacteria strains and someone asked “in laypersons terms, how will this help me if I get a bacterial infection”, it would be appropriate to clarify that it only applies to some bacteria.

[LoganDark]

> Except people don’t ask “what if I get bacteria” the way they ask about cancer.

Yeah, but doctors also don't tell people "you have bacteria" or claim "we found a cure for bacteria". The lack of nuance on average is largely due to a lack of nuance from experts. The media treats cancer as one big thing and bacteria and viruses as separate things. Thus the average joe inherits 'treating cancer as one big thing' from the media.

[dpark]

I agree with you about the media. Cancer is often presented as a monolithic thing by the media. I don’t agree at all about experts. Doctors and scientists who research cancers do not lack nuance.

[jldugger]

Is it? I'm pretty sure oncologists will say "you have stage 2 breast cancer," but I wasn't in the room at the time.

[bruce511]

I understand where you are coming from here, but I think it is helpful for people to overtly grasp that there are very different cancers, very different treatments, and indeed very different outcomes.

Without this understanding it becomes a quick jump from "we're spending all this money on cancer" to "we've made no progress"

An example of the nuance plays out in the common cancers (like breast and prostrate). These have between 90 and 100% 5 year survival rates. Others (like the one in this article, pancreatic) have very poor survivability.

As you note, it's very unlikely that we'll "cure cancer". But we already "cure" (for some definition of cure) some cancers. Progress is slow, methodical, and incremental. It can feel like a lost cause when viewed from afar, but up close very real progress is being made. And that's an important message to pass along.

[cogman10]

The other part that is simply missing is that cancer, very unfortunately, evolves and mutates. That's how you go from a cancer that responds to treatment to one that is treatment resistant.

Like you said, for a lot of common cancers we have multiple treatments. It's usually not just one magic drug, but rather the doctors working with the most effective treatments down to the least effective treatments.

[inigyou]

Depressing: evolution has discovered a universal cure for cancer, and it's reproduction. You make a whole new human without the bad bits. Other humans have to evaluate which bits are bad.

[warumdarum]

The problem is the similarities of cancer to normal cells. We have penicilin that works against all human cells. We call that poison.

Now, "no, i mean poisons that attack the special chemistry of cancer," oh yes, those we call chemo.

[cogman10]

For chemo it's often "these chemicals kills cancer cells faster than they kill regular cells".

[warumdarum]

Which is why we got ecchemo.. where the cancer affected pathways get seperated from the regular ciculatory system via shunt and then get fed the chemo seperately and get a little wash before reconnection to the full circulation. It would be even more ideal if you had the whole navel setup in two entirely seperated systems.. sorry, a man can dream..

[shevy-java]

> We have penicilin that works against all human cells.

Penicillin works against bacteria, in particular gram-positive bacteria; to a lesser extent gram-negative bacteria too (this depends on the cell membrane structure of bacteria; there are other penicillin derivatives that are also more effective on gram-negative bacteria than penicillin is, but by and large the main target will be gram-positive bacteria). It does not work against human cells. If your comparison is about drugs in general, then of course cytotoxic drugs will have an effect; simplest example I can remember off-hand is colchicin. Of course it should work against cancer cells and non-cancer cells, unless there are some mutations where colchicin could no longer bind to, but that seems very very rare, due to the natural target of colchicin involved in cellular division.

[inigyou]

It was an analogy. Just like penicillin kills a broad variety of bacteria we also know substances that kill a broad variety of cancer cells. Arsenic, for instance, and shotgun bullets. The problem is they usually select for all cells or all human cells, not cancer cells more specifically.

[shevy-java]

> I truly hope cancer will meet its "penicillin" one day (yes I know this is unlikely).

Penicillin blocks a specific enzyme (transpeptidase).

https://en.wikipedia.org/wiki/Penicillin-binding_proteins

Cancer cells, by definition, are not a uniform mass. It will depend on the cancer type, which in turn is defined by the properties those cells have. And mutations happen all the time, often more in cancer cells when their repair systems also have mutations, e. g. are less efficient. By that definition alone, there can never be a wonder-cure for all cancer types. At best you can find some proteins more important (p53 for instance) and while more than 50% of cancer cells have some form of mutation in p53, others simply don't. By that definition there will never be a penicillin-equivalent to all cancer types.

[matthewdgreen]

The correct way to read the sentence is “all cancers do not have the same causal mechanism” but people don’t talk like that because it’s off putting. Language is fluid and it’s generally on the reader to infer meaning from context. If we can do so reasonably, we do it, and we don’t need to then write additional posts chiding people over an interpretation that’s highly unlikely to be the intended one. I don’t mean to be pushy about this, btw. It’s just that pedantry can be valuable, but only if it isn’t abused.

[otabdeveloper4]

Benign cancers are a thing. They might not kill like they show in the Hollywood movies, but your quality of life will be significantly diminished.

[inglor_cz]

Squamous cell carcinoma does not metastatize, but my god it can disfigure people really badly if not treated in time.

[jibal]

> Squamous cell carcinoma does not metastatize (sic)

This is false; it does so, but slowly.

https://www.moffitt.org/cancers/squamous-cell-carcinoma/diag...

[jibal]

> Benign cancers are a thing.

No, they aren't. Cancer is malignant by definition.

There are benign non-malignant tumors.

[otabdeveloper4]

"Malignant" and "benign" isn't a dichotomy, it is a loose sliding scale.

"Benign" is any cancer where wait-and-watch is a valid medical approach.

[IshKebab]

You've been downvoted but I would say you are right. It would be more accurate to say "cancer does not have one cause".

[siva7]

It won't help... mind you this is an article from the economist. There is no such thing as a cancer "master switch", that would equal a disease master switch and that point we have solved biology.

[sarchertech]

What do you mean “it won’t help”?

It most likely will help if you get pancreatic cancer. It might help if you get one of the other types of cancers with this mutation.

And it will likely lead to new treatments for some of the worst kinds of cancer.

[GaggiX]

One of the many therapies that are being developed so that you can survive longer even with the most lethal tumours.

[mrcwinn]

Only on HN can you get content like this. What a community.

[monster_truck]

You should be thankful that they're posting about a real drug that is in human trials and yet another "in mice" pipedream